CA1078398A - Preparation of 2-diethoxyphosphinylimino-1,3-dithietane - Google Patents

Abstract

TITLE: PROCESS FOR THE PREPARATION OF
2-DIALKOXYPHOSPHINYLIMINO-1,3-DITHIETANE

ABSTRACT
There is provided a fully integrated process for preparing a 2-dialkoxyphosphinylimino-1,3-dithietane in good overall yields with considerable savings in materials, time and labor involving a plurality of steps comprising the overall reaction of a dialkoxyphosphoryl chloride and an alkali metal-or ammonium thiocyanate to obtain a dialkoxyphosphinyl isothio-cyanate, reacting the latter with 1.1 to 1.2 molar equivalents of an alkali mercaptan in the presence of a water:acetone mixture (1:9 to 1:3), and finally reacting resultant di-alkoxyphosphinyldithiocarbamate with methylene bromide or methylene iodide to obtain a 2-dialkoxyphosphylimino-1,3-di-thietane.

Description

`~` 107~398 This invention relateq to a proces~ for the pre-paration of a compound of the following foxmula:

/ P-H- ~

wherein R is Cl-C4 alkyl; characterized by the following steps (l) reacting one molar equivalent of a compound of the formula:
. R ~ R

R ~
wherein R is as above defined, with a l.0 to 1.2 molar equiva.-lent of a thiocyanate consi~ting of sodium-, pota~sium or ammonium thiocyanate at a temperature range of 5C. to 30C. to obtain a compound of the formulaL
: R0 R
/ P-NCS
Ro wherein R i8 as above defined; (2) reacting the thu~-formed com-pound without i~olation from the aboYe-said reaction mixture and in the pre~enoe of same with a l.l to 1.2 lar eguivalent of sodium or potassium hydrosulfide in a water:ace~one solvent ~ystem whexein the ratio of water:ace~one i~ establi~hed in the range of 1:3 to l:9 at a temperature range of 5C. to 30C. to obtain a compound of the formula:

~PsNR-I--S~ ~

wherein R i~ above defined and ~ i8 an alkdli metal, and (3) reacting the thus-formed compound in said water:acetone solvent Y~ .
,,~

` 1078398 system and in the presence of the reaction media with a one to

2 molar equivalent of a methylene halide consi~ting of methy-lene bromide or methylene iodide in the presence of a 1 to 2 molar equivalent of an alkàli metal bicarbonate at a temperature of 25C. to 3SC.

la -' ' .
.

107!3398 The broad spectrum contact and systemic pesti-cide, 2-diethoxyphosphinylimino-1,3-dithietanei represented by the formula (I) below:

(I) ~ 11 ~ >

and a method of preparation thereof have been disclosed in United States Patent No. 3,470,207, issued on September 30, 1969, and United States P~tent No. 3,553,319, issued on January 5, 1971. The intermediate proauct, diethoxyphosphinyl-dithiocarbamate, and a method for the preparation thereof have been disclosed in United States Patent No. 3,476,837, issued on November 4, 1969.
The aforementioned pesticide has been found to be effective for the control of soil dwelling nematodes and, especially, for the control of root-knot nematodes (Meloldo~yne incognita). Thus, it is of considerable inter-est and importance to be able to.manufacture 2-diethoxy-`~ phosphinylimino-1,3-dithietane economically on a large scale.
Unfortunately, the preparation of 2-diethoxyphos-phinylimino-1,3-dithietane, while satisfactory for small scale laboratory preparations by methods known in the art, is.not entirely suitable for large scale preparation of said compound. For comparative and illustrative purposes, one such prior art process consisting of three distinct and separate steps is hereinbelow briefly described and yraphically illustrated:
Step 1 One molar equivalent of diethoxyphosphoryl chloride . ., ~ -lb-10783g8 of formula (II) is reacted with a 1.1 to 1.2 molar equivalent of dry ammonium thiocyanate in the presence of an inert c--solvent, such as benzene, toluene, xylene or tlle like, at about 20C to 30C. The thus-obtained sQlution of diethoxy-phosphinyl isothiocyanate of formula (III) is washed several times with water and dilute sodium bicarbonate solution, and then the isothiocyanate is isolated by removing the solvent in ~acuo. This reaction step may be graphically illustrated as follows:
C2H5\11 C2H5\
P-Cl ~ NH4SCN aromatic ~-NCS + N~
2H5 solvent ~ C2tl50 (II) tIII) Step ?
The isothiocyanate of formula (III) obtained in Step 1 above, is reacted with a 1.1 to 1.2 molar equivalent of alkali metal mercaptan, such as sodium or potassium hydrosulfide, freshly prepared in situ, prior to the addition of said isothiocyanate, from hydrogen sulfide and sodium or ;~
potassium hydroxide or alkoxide te.g. t-butoxide) in a lower (Cl-C3) alcohol, to yield the corresponding diethoxyphosphinyl-dithiocarbamate of formula (IV). This reaction is quite rapid and is complete in a relatively short time. The thus-obtained dithiocarbamate of formula (IV) may be isolated if desired, but the isolation procedure is cumbersor.le, and since the dithiocarbamate is relatively unstable, it is more advantageous to use the as is reaction mixture in the following final step. This reaction step may be graphically illustrated as follows:

2}~5 \R ' C2H5o\9 P-NCS + MSH al~ohol ~P-NH-C- ~ M
2 5 ~ C2115 (III) (IV) where M is sodium or potassium.

.

~!.
Step 3' , 'To the above reaction mixture 2.5 to 10 molar equivalents of methylene bromide or methylene iodide, are added ln the presence of an acid acceptor,such as sodium S ' bicarbonate. The reaction mixture is then stirred at room temperature for rom 20 to 24 hours to yield 2-diethoxy-phosphinylimino-1,3-dithietane of formula (I). The product dithietane is isolated from the reaction mixture by 'standard laboratory procedures and purified, if necessary. This reaction step may be graphically illustrated as follows:

P-NH-C-S~ M~ + Cl~2Br2 N 3 (I~) ~ 2 5 (I) * 2MB~ + l~2 + C2 where'M is sodium or potassium.
' ' 'As hereinabove stated, this and simllar processes of the art, while suitable for small scale preparations of '~' ' 2-diethoxyphosphinylimino-1,3-dithietane, are not suitable ` 20 ' for large scale manufacturing processes. The'use of solvents, .!
'~ the relatively long reaction times required, and the need , for the purification of the intermediates coupled with the' -~ inevitable losses suffered during the work-up and purification ~ of the intermediates and of the end product make' this and ~ , . . . .
- ~5 similar approaches economically undesirable.
' Surprisingly, it has been found that the désired 2-diethoxypllosphinylimino-1,3-dithietane o~ formula ~I) may be conveniently prepared in excellent overall yields by the novel fully integrated process of the present invention. The ' term "fully integrated process" is employed to indicate that iP this process the hereinabove described individual reaction steps leading to the desired formula (I) dithietane .
-- 3 .

.. . . .. . .. ~

1C378;398 are combined into one continuous and interlocking sequence of reactions, whereby either the need to isolate or purify the intermediates in both is eliminated. Rather, the as-is reaction mixtures containing intermediates and any by-products and impurities formed in the reaction, are used in each subsequent step of the process. Additionally, the reaction times for each step are shortened without adverse affect on yields; and the product: 2-diethoxyphosphinylimino-1,3-dithietane is obtained in excellent overall yields.
The fully integrated process of the present invention is hereinbelow described and graphically illustrated in detail:
Step 1 One molar equivalent of diethoxyphosphoryl chloride of formula (II) above is reacted neat with a 1.0 to 1.2 molar equivalent of sodium, potassium or arnmonium thiocyanate at a temperature range of 5C to 30C and, preferably, 15C to 25C for a period of time from 2 to 4 hours to yield diethoxyphosphinyl isothiocyanate of formula (III), above.
The reaction is slightly exothermic, easily controlled by a cooling bath.
The as-is reaction mixture containing the isothio-cyanate of formula (III) is used without delay in the follow-ing step.
Step 2 The reaction mixture of Step 1 containing the iso-thiocyanate of formula (III) is added slowly to a water:acetone mixture containing 1.1 to 1.2 molar equivalents of sodium or potassium hydrosulfide wherein the ratio of water:acetone is established in the range of 1:9 to 1:3 and, preferably, in the ratio of 1:3, at a ter,lperature ranging from 5C to 25C. The reaction is exothermic. It is controlled by means of a suitable cooling bath. The reaction is rapid and is complete in about 10 to 15 minutes after ~he a~ditio~
of the Step 1 reaction mixture is completed. The reaction mixture of Step 2 containing diethoxyphosphinyldithio-carbamate i~ utilized in the final step of the process.

Step 3 One to 2.0 molar equivalent of a methylene halide such as methylene bro~ide, or methylene iodide, and one to two molar equivalents of ~sodium bicarbonate are added to the Step 2 reaction mixture. Resultant slurry is stirred at about 20C to 30C and, preferably, at 25C for from about 4 hours to 8 hours and, preferably, for 6 hours.
Acetone is next stripped from the reaction mixture and the . .
product extracted with an arornatic solvent such as toluene. ' The thus-obtained solution of 2-diethoxyphosphinylimino-1 1,3-dithietane is washed with water and dilute sodium bicarbonate solution and the product is isolated, if desired, by remo~ing the aromatic solvent in vacuo.
. The preferred embodiment of the above-described fully integrated process may be graphically illustrated as follows: -C2~5 \11 2 5 \ ~1 P-Cl + NaSCN ~ nea~ ~ P-NCS ~ NaCl 2 5 tII) ~. 2 5 (III) (III) ~ NaSH ater a t e (1 3) C2~5~ll NH~ S~ a~
; ~ - 3 C2~1~0 ~ (IV) (IV)+ C112Br~ wa~er:ilcetonc (1:3)? S
+ NallC03 C2T15~ + C02 (~?
By the above ~ully inte~rated process formula (I) product is obtained in 60~ to 68% ~verall yields.

... ....... . .

1~78398 - It has been unexpectedly found that the methylene halide reactant of Step 3 may be introduced in Step 1 of the above described fully integrated process. This seemingly minor change in the overall process is quite significant and of marked advantage on a large scale. First, the above-identified thiocyanates are hygroscopic and thus tend to absorb moisture from the air while being added to the diethoxyphosphoryl chloride and thus normally would require protective blanketing with an inert dry gas, such as nitrogen, 0 and special equipment to load the reactor, since the presence of even small amounts of water significantly reduce the yields of this reaction step. The use of the above-identi-; fied methylene halide reactant of Step 3 as an inert diluent and reaction medium in Step 1 allows for the rapid introduc-tion of the thiocyanate into the reactor with minimum exposure to air and the moisture contained therein and, thereafter, said methylene halide serves as a protective liquid blanket preventing said thiocyanate from absorbing ~; moisture from the air. This eliminates the need for the use of special equipment as well as an inert gas during the addition of said thiocyanate.
Advantageously, the aforementioned change allows for the addition of liquid diethoxyphosphoryl chloride in a closed system to the stirred thiocyanate_methylene halide mixture. Since the resultant reaction is exothermic, the exotherm is easily controlled by adjusting the rate of addition of the phosphoryl chloride. Additionally, as an inert diluent, the methylene halide allows ~or a more thorough stirring, mixing and pumping of an otherwise thick reaction mixture. Thus, there is not any need to employ special high powered stirring and pumping equipment and, therefore, additional savings in energy requirements can be 1(~78398 realized. Clearly, the methylene halide is present in Step 2. However, in Step 3 it becomes a reactant and such modi-fication does not affect the overall yield.
It has further been found that where the herein-above defined water:acetone ratios are not used, the yields of formula CI) product are significantly reduced.
Substitution of bromochloromethane or methylene chloride for methylene bromide (or iodide) in the above fully integrated process also results in significantly reduced yields of 2-diethoxyphosphinylimino-1,3-dithietane and is not preferred herein.
In general, analogs of formula (I), namely, 2-di- ~
j ethoxyphosphinylimino-1,3-dithietane, represented by formula: ~ -<S .
R0 :. !`'.
wherein R is selected from the group consisting of methyl, propyl, isopropyl and butyl, are contemplated. These can be prepared by the novel fully integrated process of the present invention.
The desired 2-diethoxyphosphinylimino-1,3-dithietane having nematocidal properties may be formulated as liquid or emulsifiable concentrates, wettable powders, dusts, dust concen-trates and granular formulations according to the needs and demands of the users thereof.
The following examples further illustrate the invention.
Example 1 Preparation of 2-Diethoxyphosphinylimino-1,3-dithietane Ammonium thiocyanate (67.0 g; 0.88 mole) is added at 5C to diethoxyphosphoryl chloride (138.0 g; 0.80 mo~).
The resulting thick slurry is stirred at 25C for 4 hours, *hen is cooled to 5C and treated with chilled water (175 ml).
A two phase system forms and is stirred for 3 minutes and then the bottom organic phase consisting of diethoxyphosphinyl isothiocyanate is separated.
The diethoxyphosphinyl isothiocyanate obtained in the above step is then added dropwise at 10C to a solution of sodium hydrosulfide monohydrate (74.0 g - 73~ real;
1.0 mole) in water (96 ml) and acetone (328 ml) while main-taining the reaction temperature below 25C in an ice bath.
Ten minutes after the addition is completed, sodium bicar-bonate (134.4 g; 1.6 mole) and methylene bromide (139.1 g;
~ 0.80 mole) are added to the reaction mixture and the resulting ; slurry is stirred at 25C for 16 hours.
The acetone is then stripped from the reaction mix-ture and toluene (400 ml) added to the residue. The toluene slurry is stirred with water (240 ml) to dissolve most of the solids. The two phase reaction mixture is then filtered and the aqueous phase separated. The toluene phase is washed with saturated aqueous sodium bicarbonate solution (240 ml) and is then evaporated to constant weight under vacuum to yield 142.0 g (86.5% real, 63.9% yield) of 2-diethoxyphos-phinylimino-1,3-dithietane.
The above process is repeated, except that the diethoxyphosphinyl isothiocyanate obtained in the first step is not isolated. Rather, the as-is reaction mixture con-taining the isothiocyanate is used immediately in the next step of the process and in the third step,the reaction is terminated in 6 hours.
Substitution of dimethoxyphosphoryl chloride, diisopropoxyphosphoryl chloride or di-_-butoxyphosphoryl chloride for diethoxyphosphoryl chloride in the above example yields 2-dimethoxyphosphinylimino-1,3-dithietane, ~078398 2-diisopropoxyphosphinylimino-1,3-dithietane or 2-di-_-butoxyphosphinylimino-1,3-dithietane, respectively.
Example 2 Preparation of 2-Diethoxyphosphinylimino-1,3-dithietane Diethoxyphosphoryl chloride (138.0 gi 0.80 mole) is added at 5C to a stirred mixture of dry ammonium thio-cyanate (67.0 g; 0.88 mole) and methylene bromide (139.1 g;
0.80 mole), and the resulting reaction mixture is stirred ;, at 25C for 4 hours.
The above reaction mixture, containing the inter-, mediate diethoxyphosphinyl isothiocyanate, is then added slowly at 10C to a solution of sodium hydrosulfide mono-f' hydrate (74.0 g - 7396 real; 1.0 mole) in water (96 ml) and i acetone (328 ml) while maintaining the reaction temperature ;~ below 25C in an ice bath. Ten minutes after the addition is completed, sodium bicarbonate (134.4 g; 1.6 mole) is added ;' to the reaction mixture and the resulting slurry is stirred at 25C for 6 hours.
The acetone is then stripped from the reaction mix-ture and toluene (400 ml) added to the residue. The toluene slurry is stirred with water (240 ml) to dissolve most of the solids. The two phase reaction mixture is then filtered and the aqueous phase separated. The toluene phase is washed with saturated aqueous sodium bicarbonate solution (240 ml) and is then evaporated to constant weight under vacuum to yield 2-diethoxyphosphinylimino-1,3-dithietane.
E:xample 3 This example illustrates the effect of water:acetone ratios on the yield of 2-diethoxyphosphinylimino-1,3-dithie-tane.
The process OI' ~ xample 1 is repeated except that in Steps 2 and 3 the water:acetone ratios are varied. The water:acetone ratios and yields are summarized in Table I
below:
Table I
Parts by VolumePercent Yield of Theory Water:acetone Ratios 0 (No acetone)49.4 50:1 53.1 10:1 59.2 It can be seen from Table I that the overall yields of the process decrease as the volume of water in the water:acetone mixture is increased beyond the 1:3 to 1:9 range.

Example 4 This example illustrates the effect of water:acetone ratios on the yield of 2-diethoxyphosphiny-limino-1,3-dithie-tane when utilizing Step 3 reactlon of the process of the present invention.
A mixture of methylene bromide (8.7 g; 0.05 mole), sodium bicarbonate, acetone and water is stirred rapidly at 10C and potassium diethoxyphosphinyldithiocarbamate added over 10 minutes. The temperature of the reaction mixture is adjusted to 25C and the reaction is allowed to stir for 25 hours.
The acetone is then stripped from the reaction mixture and toluene (25 ml) added to the residue. The two phase reaction mixture is separated. The toluene phase is washed with saturated aqueous sodium chloride (50 ml), then with saturated aqueous sodium bicarbonate (50 ml) and satu-rated aqueous sodium chloride (50 ml). The toluene phase is then evaporated to constant weight under vacuum to afford 2-diethoxyphosphinylimino-1,3-dithietane. The water:acetone ratios and the yields are summarized in Table II below:

1~78398 Table II
Parts by Volume Percent Yield of Theory Water:acetone Ratio 1:20 64.8 1:40 63.36 1:7 74.34 1:3 72.18 It can be seen from Table II that the yields in Step 3 of the process decrease as the volume of the acetone in the water:acetone mixture is increased beyond the 1:3 to 1:9 range.
Example 5 Evaluation of 2-DiethoxyphosPhinylimino-1,3-dithietane for the control of root-knot nematode (Meloidogyne incognita) on tomato in the greenhouse A. Material ; 2-Diethoxyphosphinylimino-1,3-dithietane.
B. Plant Tomato (Lycopersicon esculentum; cv. Bonny Best).
C. Infective Agent Root-knot Nematode (Meloidogyne inco~nita) inoculum.
Application Rates/Liter of Potting Soil (Equivalent to Pound/Acre - Broadcast) 2-Diethoxyphosphinylimino-1,3-dithietane at 0.75 mg, 1.5 mg and 3.0 mg/liter of soil.
Procedure Acetone solutions of the sample are prepared at the appropriate concentrations. One liter of moist potting soil is placed in a suitable stainless steel beaker. One ml of candidate solution is distributed, drop by drop, over the surface of the soil. The beaker is then capped and placed on an off-center rotary mixer and mixed for 2 minutes (about 107839~ .

60 revolutions). After mixing, the soil is divided between two 0.5 liter paper cups by filli~g the cups half full of soil then distributing 25 ml root-knot nematode inoculum on the soil and filling the remainder of the container with treated soil. Seedling tomato plants are transplanted into the cups of soil the same day, watered and removed to the greenhouse.
After about 4 weeks, the tomato plants are carefully removed from the containers, the soil washed away from the roots, and the roots are then examined for nematode galling.
The roots are indexed for galling by the following system:
0 = No visible galling.
T = Less than 1% of roots with galls.
1 = 1-5% of roots galled.
2 = 6-10% of roots galled.

3 = 11-20% of roots galled.

4 = 21-30% of roots galled.

5 = 31-40% of roots galled.

6 = 41-50% of roots galled.
20 ~ 7 = 51-60% of roots galled.
8 = 61-70% of roots galled.
9 = 71-80% of roots galled.
10 = 81-100% of roots galled.
The result5 obtained are summarized in Table III
below.

1078398 :, i .. l ,o~ l,~
o~
a) ~.o c~ o o 0~ I~ero ~ O

a ~ ~
.,,," , ~ ~ 0 X
~ ~ ~ ~ u)~ E~ ~o o S O H . : .
8 o~ ~ ~o o o ,~ ~a ~ ;:
I ~ o ~ ~o o o E O P~ ~1 i ~1 ~1 a) ~ u~
R ~ ~ ~ ~ o E~ .~ ~ P~ o~ l l ~: ' ,~, v E .~
~ X ,~ ,1 ~ ~ ~:: ~ u~ h .
O O rC ~ ~
O O
e 8 o ~ ~ c~
o a) c~ s 0 ~ ~
~o ~ X-~ o ~o SS ~a a 0 ,Y ~ ~1 a) ~ ~> "
.,, I a~ l 0~ oO a ~ ~ o Z

Claims (5)

1. A process for the preparation of a compound of the formula:

wherein R is C1-C4 alkyl; characterized by the following steps (1) reacting one molar equivalent of a compound of the formula:

wherein R is as above defined, with a 1.0 to 1.2 molar equivalent of a thiocyanate consisting of sodium-, potassium or ammonium thiocyanate at a temperature range of 5°C. to 30°C. to obtain a compound of the formula:

wherein R is as above defined; (2) reacting the thus-formed compound without isolation from the above-said reaction mixture and in the presence of same with a 1.1 to 1.2 molar equivalent of sodium or potassium hydrosulfide in a water:acetone solvent system wherein the ratio of water:ace-tone is established in the range of 1:3 to 1:9 at a temper-ature range of 5°C. to 30°C. to obtain a compound of the formula:

wherein R is as above defined and M is an alkali metal, and (3) reacting the thus-formed compound in said water:ace-tone solvent system and in the presence of the reaction media with a one to 2 molar equivalent of a methylene halide consisting of methylene bromide or methylene iodide in the presence of a 1 to 2 molar equivalent of an alkali metal bi-carbonate at a temperature of 25°C. to 35°C.

2. The process according to Claim 1, wherein R is ethyl; the thiocyanate is ammonium thiocyanate and the reac-tion temperature is 25°C.; the hydrosulfide is sodium hydro-sulfide, the ratio of water:acetone in the solvent system is 1:3, and the reaction temperature is 25°C.; the methylene halide is methylene bromide, and the reaction temperature is 25°C.

3. The process according to Claim 1, wherein the thiocyanate is sodium thiocyanate.

4. The process according to Claim 1 wherein a methylene halide is added in step 1 of the process.

5. The process according to Claim 4, wherein the thiocyanate is sodium thiocyanate.